Gambogenic acid

Cancer: Breast
Action: Overcomes MDR, Adriamycin
Adriamycin (ADR) is beneficial for the treatment of breast cancer. However, its wide application often leads to drug resistance in clinic practice, which results in treatment failure. Gambogenic acid (GNA), a polyprenylated xanthone isolated from the traditional medicine gamboge, has been reported to effectively inhibit the survival and proliferation of cancer cells.
An MTT assay was used to evaluate the inhibitory effect of the drugs on the growth of MCF-7 and MCF-7/ADR cell lines. The effects of drugs on apoptosis were detected using Annexin-V APC/7-AAD double staining. The expression of apoptosis-related proteins and the proteins in the PTEN/PI3K/AKT pathway were evaluated by Western blot analysis.
In the MCF-7/ADR cell lines, the IC50 (half maximal inhibitory concentration) of the group that received combined treatment with GNA and ADR was significantly lower than that in the ADR group, and this value decreased with an increasing concentration of GNA. In parallel, GNA treatment increased the chemosensitivity of breast cancer cells to ADR. T
The study by He et al., (2015) has indicated a potential role for GNA to increase the chemosensitivity of breast cancer cells to ADR. This modulatory role was mediated by suppression of the PTEN/PI3K/AKT pathway that led to apoptosis in MCF-7/ADR cells. This work suggests that GNA may be used as a regulatory agent for treating ADR resistance in breast cancer patients.
Source
He Y, Ding J, Lin Y, et al. Gambogenic acid alters chemosensitivity of breast cancer cells to Adriamycin. BMC Complementary and Alternative Medicine 2015, 15:181 doi:10.1186/s12906-015-0710-8

 

Cancer: Lung
Action: Autophagy
Gambogenic acid (GNA) is one of the active compounds of Gamboge, a traditional medicine that was used as a drastic purgative, emetic, or vermifuge for treating tapeworm. Recently, increasing evidence has indicated that GNA exerts promising anti-tumor effects. In the present paper, Mei et al., (2014) found that GNA could induce the formation of vacuoles, which was linked with autophagy in A549 and HeLa cells. Further studies revealed that GNA triggers the initiation of autophagy based on the results of MDC staining, AO staining, accumulation of LC3 II, activation of Beclin 1 and phosphorylation of P70S6K. Similar results were obtained using a xenograft model. Their findings show, for the first time, that GNA can cause aberrant autophagy to induce cell death and may suggest the potential application of GNA as a tool or viable drug in anticancer therapies.
Source
Mei W, Dong C, Hui C, Bin L, Fenggen Y, Jingjing S, et al. (2014) Gambogenic Acid Kills Lung Cancer Cells through Aberrant Autophagy. PLoS ONE 9(1): e83604. doi:10.1371/journal.pone.0083604

 

Cancer: Triple Negative Breast
Action: Decrease bcl-2, inhibited cell proliferation, apoptosis
Zhou et al., (2013) used nude mouse models to detect the effect of gambogenic acid on breast tumors, analyzing expression of apoptosis-related proteins in vivo by Western blotting. Effects on cell proliferation, apoptosis and apoptosis-related proteins in MDA-MB-231 cells were detected by MTT, flow cytometry and Western blotting. Inhibitors of caspase-3,-8,-9 were also used to detect effects on caspase family members.
They found that gambogenic acid suppressed breast tumor growth in vivo, in association with increased expression of Fas and cleaved caspase-3,-8,-9 and bax, as well as decrease in the anti-apoptotic protein bcl-2. Gambogenic acid inhibited cell proliferation and induced cell apoptosis in a concentration-dependent manner.
Gambogenic acid suppressed breast cancer MDA-MB-231 cell growth by mediating apoptosis through death receptor and mitochondrial pathways in vivo and in vitro.
Source:
Zhou J, Luo YH, Wang JR, Lu BB, Wang KM, Tian Y. Gambogenic acid induction of apoptosis in a breast cancer cell line. Asian Pac J Cancer Prev. 2013;14(12):7601-5.